The overall objective of the proposed studies is to investigate whether malaria disease is worsened or made less severe by concurrent or previous parasitic (helminths) worm infections. Our hypothesis is that worms can affect the incidence and severity of malaria. This hypothesis seems plausible since a large portion of the population living in malaria endemic areas are also infected with helminths, and it seems fair to suggest that immunity to malaria is influenced by worm infections. Therefore the manipulation of anti-malarial immunity, treatment and other control measures must be accompanied by an understanding of the role of worms in influencing malaria disease. It is not possible to adequately address these questions in humans due to ethical and other considerations;however we can carry out carefully controlled investigations in suitable animal models. The studies proposed here will be carried out in a primate model (the Olive baboon) that is a model of both infections and, unlike rodent models, is ideal for long-term studies of malaria and schistosomiasis. We hope to gain a better understanding in two major areas of co-infection: First, if schistosomiasis makes malaria worse, then administration of a single cheap dose of anti- helminthic drug such as Praziquantel could markedly affect malaria outcomes. Thus one of our specific aims is to treat schistosome infections and then do a detailed follow-up on malaria infection rate and symptoms in order to establish the precise effect of helminth infections on severe malaria disease. Depending on the outcome of our studies (i.e. less or worse malaria in schistosomiasis-infected animals) recommendations can be made on whether helminth control should be integrated with malaria control. Secondly, the analysis of the immunological parameters that accompany co-infection with malaria and schistosomes will shed more light on the mechanisms of acquired immunity that is responsible for partial resistance to malaria observed in people living in endemic areas. PUBLIC HEALTH RELEVANCE: Many people living in Africa and elsewhere in the tropics suffer from combined malaria and parasitic worm infections. It is unclear whether the presence of worms makes malaria disease worse or less severe. We propose to unravel this question by conducting experiments in a primate (baboon) model of both malaria and schistosomiasis infections.